Redermalization in the correction of skin aging

Aging factors and cellular processes

Aging is a gradual accumulation of defects in DNA molecules, increasing disorganization of physiological processes in the cell, accumulation of damage, which ultimately lead the body to death. Skin aging is only one of the elements of the aging of the body as a whole.

Aging is influenced by many factors, which can be divided into two large groups:

• internal factors : heredity, chronic diseases, dysfunction of the immune and hormonal systems;
• external factors : UV radiation, ecology, stress, smoking, alcoholism, drug addiction, poor nutrition, etc.

For a long time, scientists have been trying to understand the causes of aging, proposing various theories. Today, Harman's free radical theory and Maillard's theory of glycation are generally accepted.

Harman's free radical theory explains the aging process by the excessive formation of free radicals and their influence on cellular metabolic processes. There are various reasons for the formation of free radicals, but no matter what the reason is, they damage the genetic apparatus of the cell, thereby causing harm to the body as a whole.

According to Maillard's theory of glycation, aging can develop as a result of a non-enzymatic reaction of monosaccharides with amino groups of proteins, resulting in the formation of so-called collagen cross-links. Such collagen is not destroyed by collagenase, and collagen crosslinks accumulate in the dermis. The rate of this reaction depends on the concentration of sugars and time, and it increases sharply in the presence of free radicals. In turn, free radicals, affecting cell proteins, make them less protected from the effects of sugars.

During evolution, an antioxidant defense system has been developed, including superoxide dismutase, catalase, and peroxidase. Mitochondria play an important role in preventing the formation of reactive oxygen species. They perform the function of specialized energy centers. In the respiratory chain of mitochondria, during the process of oxidative phosphorylation (the Krebs cycle, which occurs inside mitochondria), the energy of various compounds is transformed into the energy of phosphate bonds of ATP. The Krebs cycle is shown schematically in Figure 1. Without going into biochemical details, let’s say that one of the necessary elements of this cycle is sodium succinate (sodium salt of succinic acid). In addition, mitochondria have their own genetic apparatus, which determines their relative independence from the cell nucleus. Changes in the mitochondrial genome are one of the most important mechanisms that determine cell aging in particular and the aging of the body in general.

Skin aging

The aging processes occurring in the body are reflected in the most deplorable way on the skin. The processes occurring in aging skin can be succinctly characterized as follows. The amount of water in the epidermis decreases, which leads to disruption of keratinization and slower desquamation of the epithelium. As a result of this, the epidermis becomes thinner, but at the same time its stratum corneum thickens and becomes denser, a network of fine wrinkles is formed, pigment spots and dilated capillaries appear. In the basal layer of the epidermis, mitosis and differentiation of new cells are disrupted, which, in turn, leads to a slowdown in the movement of keratinocytes to the surface of the skin. As a result, the rate of renewal of the epidermis decreases and the barrier function of the skin is weakened.

During the aging process of the dermis, fibroblasts are damaged, the synthesis of collagen, elastin, and GAGs slows down, lipid peroxidation of cell membranes develops, glycation processes increase, and all layers of the skin become thinner.

Basis of biorevitalization

One of the tasks of aesthetic medicine is to find new effective methods for correcting signs of aging. In 2000, Professor Di Pietro (Italy) proposed a technique for intradermal injections of hyaluronic acid preparations in order to restore the intercellular substance and water balance, as well as stimulate the differentiation of fibrocytes into fibroblasts. As a result, the formation of collagen, elastin, and glycosaminoglycans is stimulated. The method is called biorevitalization. It is widely recognized in the world of aesthetic medicine.

Currently, there are more than 10 varieties of hyaluronic acid preparations for biorevitalization on the Ukrainian market, and these preparations are actively used by dermatocosmetologists.

Hyaluronic acid (HA) was first isolated by K. Mayer and J. Palmer in 1934 from the vitreous humor of a cow's eye. The name comes from the Greek “hyalos” - glassy and the words “uronic acid”, a component of this polysaccharide. The molecular weight of HA is 10,000 kDa. It is presented in almost all tissues. The HA content in the dermis is 0.5 mg/g, in the epidermis – 0.1 mg/g. HA synthesis occurs on the inner surface of the plasma membrane of fibroblasts. As the chain forms, HA is released through the membrane to the outer surface of the cell. HA is the most rapidly renewed component of the extracellular matrix; The lifespan of a hyaluronic acid molecule is only a few days.

Hyaluronic acid is unique due to its physical and chemical properties. It is a polysaccharide containing hydrophobic and hydrophilic regions. Being a polyanion in structure, HA is capable of binding and retaining large amounts of water through hydrogen bonds. Moreover, the higher the molecular weight of HA, the more moisture it attracts. This ability does not change even when the concentration of water in the surrounding space decreases. HA is found in the extracellular matrix, on the cell surface and inside cells.

The ability of HA to form highly viscous aqueous solutions, complexes with proteins, participate in the transport and distribution of water, in ion exchange, the formation of the extracellular matrix, provide selective tissue permeability, and maintain migrating cells in a state of dispersion indicates the important role of HA in maintaining intercellular and cellular homeostasis.

Combination of HA and sodium succinate

As mentioned above, with age, the amount of hyaluronic acid in the skin noticeably decreases, and this is one of the reasons for the visible manifestations of aging.

The study of the pathogenesis of the aging process has shown that three key links can be distinguished in it:

• loss of moisture;
• oxidative stress – the damaging effects of free radicals;
• decreased activity of tissue respiration and metabolic processes in tissues.

Hyaluronic acid preparations actively affect the first link, replenishing moisture loss. The second and third links of pathogenesis are affected by biorevitalization to a much lesser extent. Scientists found a way out of the situation: they added sodium succinate to the injection drug in addition to hyaluronic acid, creating a new drug that entered the market in 2009. The method of restoring functions in the aging dermis was called redermalization.

Sodium succinate, being a substrate in the Krebs cycle, which occurs in mitochondria, directly affects the production of ATP, functions as a regulator of physiological and biochemical processes, and activates tissue respiration. In addition, succinate has powerful antioxidant properties (Table 1).

Table 1. Basic properties of HA and sodium succinate

Thus, the use of a new generation drug, which consists of hyaluronic acid and sodium succinate, makes it possible to influence various pathogenetic mechanisms of skin aging and achieve a powerful complex anti-age effect from redermalization.

From theory to practice

Under the leadership and with the assistance of the Department of Dermatovenereology of the National Medical Academy of Postgraduate Education (head of the department, Doctor of Medical Sciences, Professor L. D. Kalyuzhnaya), a series of redermalization procedures were carried out. Number of patients – 126, age – from 40 to 60 years, gender – female. The number of procedures is 3–4 with an interval of 2 weeks. The procedures were performed using linear and papular techniques. The effect was visible after the first procedure. All patients noted a feeling of “fullness” of the skin and a lifting effect, which increased by the 3rd–4th procedure. The complexion was revitalized, small wrinkles were smoothed out, and the depth of large wrinkles was reduced. There were no cases of drug intolerance.

It should be noted that the papules on the face resolved within 1–3 days, and the process of resorption accelerated with each subsequent procedure. On the skin of the neck and décolleté, papules resolved more slowly, in about 5–7 days.

Thus, the use of hyaluronic acid with sodium succinate is indicated for the effective implementation of anti-age programs.

This article is part of the special project Global anti-aging

You can read all the articles on this topic:

SPECIAL PROJECT. Global anti-aging

Literature:

• Irina Medvedeva is a dermatovenerologist of the highest category, Candidate of Medical Sciences, Honored Doctor of Ukraine, President of the All-Ukrainian Association of Specialists in Applied Aesthetics (Ukraine, Kyiv).
• KOSMETIK international journal, No. 2(40), 2010